Table 1.
Population parameter estimates for vildagliptin pharmacokinetics
| Parameter (units) | Definition | Estimate | BSV (%) | SE†(%) |
|---|---|---|---|---|
| CL (l h–1) | Non-saturable vildagliptin clearance | 36.4 | 25 | 9 |
| VC (l) | Volume of central compartment | 22.2 | 37 | 11 |
| VP (l) | Volume of tissue compartment | 97.3 | 37 | 13 |
| CLic (l h–1) | Intercompartmental clearance | 40.1 | 34 | 11 |
| ka1 (h−1) | Absorption rate constant | 1.26 | 46 | 15 |
| ka2 (h−1) | Absorption rate constant | 1.05 | 14 | 4 |
| F (%) | Bioavailability | 77.2* | – | – |
| Kd (nmol l–1) | Equilibrium dissociation constant | 71.9 | 54 | 16 |
| k2 (h−1) | Rate constant for conversion of weak complex to high-affinity complex | 23.4 | 70 | 22 |
| koff (h−1) | Dissociation rate constant of intact vildagliptin from DPP-4 | 0.612 | 94 | 27 |
| kdeg (h−1) | Rate constant for hydrolysis of vildagliptin by DPP-4 | 0.110 | 81 | 26 |
| RmaxC (nmol) | DPP-4 in VC | 5.0 | 12 | 4 |
| RmaxP (µmol) | DPP-4 in VP | 13.0 | 64 | 23 |
| cf1 mU ml−1 min−1 nmol−1 | Conversion factor between free DPP-4 enzyme and observed DPP-4 activity | 2.80 | 17 | 5 |
| CVVilda (%) | Proportional error for vildagliptin | 48.7 | ||
| SDVilda (ng ml–1) | Additive error for vildagliptin | 0.99 | ||
| CVDPP-4 (%) | Proportional error for DPP-4 activity | 19.6 | ||
| SDDPP-4 (mU ml–1 min−1) | Additive error for DPP-4 activity | 0.061 |
*
Fixed to the estimate from the model including i.v. vildagliptin data.
†
Standard errors (SE) were obtained by bootstrap method 1 as implemented in S-ADAPT and are reported as coefficients of variation (%). Standard errors for BSV parameter estimates were between 25 and 57%.